1.Human umbilical cord mesenchymal stem cells co-culture ameliorates the innate immunity of podocytes induced by high glucose
Yinghui WANG ; Shasha LYU ; Yan SONG ; Jing CHENG ; Shanshan LIU ; Yaping ZHANG ; Long ZHAO ; Xueling WANG ; Lina SUN ; Gang LIU
Chinese Journal of Nephrology 2017;33(11):849-855
Objective To explore the effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on the innate immunity of podocytes mediated by Toll-like receptor (TLR)signaling pathway under high glucose (HG) condition.Methods Podocytes were divided into four groups according to the treatment:normal glucose group (NG),mannitol control group (NG+MA),high glucose group (HG) and HUC-MSCs co-culture group (HG+MSC).After 72 hours treatment,the protein levels of interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),heat shock protein 70 (HSP70),high-mobility group box-1 (HMGB1)in culture medium were measured by ELISA.Real-time PCR was used to detect the mRNA expressions of TLR2 and TLR4.Western blotting was used to detect the protein expressions of TLR2,TLR4,myeloid differentiation factor 88 (MyD-88) and phospho-P65 (p-P65).Immunofluorescence staining was used to study the localization of p-P65 in podocytes.Results High glucose induced the inflammation of podocytes by activating the TLR signaling,which increased the secretion of IL-6,TNF-α,HSP70,HMGB1,the mRNA level of TLR2,TLR4 and the protein level of TLR2,TLR4,MyD-88 and p-P65 (all P < 0.05).High glucose also activated NF-κB and induced its nuclear translocation.HUC-MSCs co-culture decreased the inflammation and restrained the TLR signaling.Conclusions HUC-MSCs co-culture decreases the inflammation and innate immunity of podocytes induced by HG.
2.Short-term efficacy and safety of Donafenib as postoperative adjuvant therapy for patients with high risk of recurrence after radical resection of hepatocellular carcinoma: a multicenter retrospective study
Jianhua RAO ; Xinhua ZHU ; Hongwei ZHANG ; Shaochuang WANG ; Xin WEI ; Yonghua XU ; Long ZHANG ; Zhengfeng XUAN ; Yongquan CHI ; Feng ZHANG ; Xuehao WANG ; Ling LYU ; Feng CHENG
Chinese Journal of Digestive Surgery 2023;22(12):1433-1443
Objective:To investigate the short-term efficacy and safety of Donafenib as postoperative adjuvant therapy for patients with high risk of recurrence after radical resection of hepatocellular carcinoma (HCC).Methods:The propensity score matching (PSM) and retrospective cohort study was conducted. The clinicopathological data of 157 HCC patients with high risk of recurrence after radical resection who were admitted to 6 medical centers, including The First Affiliated Hospital of Nanjing Medical University et al, from June 2021 to February 2023 were collected. There were 128 males and 29 females, aged (59±10)years. Of 157 patients, 101 cases undergoing Donafenib as postoperative adjuvant therapy were divided into the the Donafenib group, and 56 cases under-going no systemic postoperative adjuvant therapy were divided into the control group. Observation indicators: (1) PSM and comparison of general data of patients between the two groups after matching; (2) postoperative treatment; (3) follow-up and survival of patients; (4) analysis of risk factors affecting recurrence-free survival of patients. PSM was done based on the principle of optimal perfect matching, with the clamp value of 0.5, and the Donafenib group and the control group were matched at a ratio of 1.25∶1. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers and/or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Kruskal-Wallis H test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and the Log-Rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Results:(1) PSM and comparison of general data of patients between the two groups after matching. Of 157 patients, 126 cases were successfully matched, including 70 cases in the Donafenib group and 56 cases in the control group, respectively. The elimination of tumor number confounding bias ensured comparability between the two groups after PSM. (2) Postoperative treatment. After PSM, of 70 patients in the Donafenib group, there were 23 cases receiving Donafenib monotherapy, 26 cases combined with transcatheter arterial chemoembolization (TACE), 14 cases combined with immunotherapy, and 7 cases combined with TACE+immunotherapy. Of 56 patients in the control group, there were 37 cases receiving postoperative follow-up alone and 19 cases combined with TACE. (3) Follow-up and survival of patients. All 157 patients were followed up, and the follow-up time of the 101 patients in Donafenib group and the 56 patients in control group were 10.1(range, 6.3-14.6)months and 22.2(range, 15.1-25.5)months, respectively. During the follow-up period, 70 patients in the Donafenib group experienced treatment-related adverse reactions, inclu-ding 8 cases of grade 3 adverse reactions, 23 cases of grade 2 and 39 cases of grade 1 adverse reactions, respectively. After PSM, the postoperative 12-, 18-month recurrence-free survival rates were 83.7%, 83.7% in the 70 patients of Donafenib group and 67.8%, 58.9% in the 56 patients of control group, respectively, showing a significant difference in the postoperative recurrence-free survival time between the two groups ( hazard ratio=0.395, 95% confidence interval as 0.176-0.888, P<0.05). (4) Analysis of risk factors affecting recurrence free survival of patients. Results of multivariate ana-lysis showed that microvascular invasion, vascular thrombus, clinical stage as ⅢA were independent risk factors affecting recurrence-free survival in patients with high risk of recurrence after radical resection of HCC ( hazard ratio=2.181, 2.612, 2.612, 95% confidence interval as 1.028-4.629, 1.128-6.047, 1.128-6.047, P<0.05), Donafenib as postoperative adjuvant therapy was an independent protective factor affecting recurrence-free survival in patients with high risk of recurrence after radical resection of HCC ( hazard ratio=0.457, 95% confidence interval as 0.227-0.920, P<0.05). Results of further analysis showed that after PSM, there were significant differences in the postoperative recurrence-free survival time in patients with different clinical factors, including male, age ≥60 years, tumor diameter >5 cm, positive microvascular invasion, positive hepatitis B virus infection, alpha fetoprotein <200 μg/L, between the Donafenib group and the control group ( hazard ratio=0.283, 0.202, 0.174, 0.345, 0.273, 0.180, 95% confidence interval as 0.114-0.707, 0.044-0.937, 0.038-0.794, 0.128-0.929, 0.091-0.819, 0.052-0.620, P<0.05). Conclusion:Donafenib as postoperative adjuvant therapy can effectively reduce the short-term recurrence rate in patients with high risk of recurrence after radical resection of HCC, with good safety and tolerance.
3.Effect of Yttrium-90 microsphere transarterial radioembolization for unresectable primary liver cancer:a Meta-analysis
Muxing LI ; Xufeng ZHANG ; Jiwen CHENG ; Ying ZHU ; Wanli WANG ; Jian DONG ; Zhida LONG ; Yi LYU
Chinese Journal of Hepatic Surgery(Electronic Edition) 2014;(6):26-30
ObjectiveTo assess the effect of transarterial radioembolization (TARE) using Yttrium-90 microsphere for unresectable primary liver cancer (PLC).MethodsLiterature from January 2009 to December 2013 were searched in the Medline, Web of Science, Cochrane Controlled Trial Register (CENTRAL) and EMBASE databases with the search terms mainly including: radioembolization, transarterial radioembolization, TARE, selective internal radiation therapy, SIRT, Yttrium-90, 90Y, chemoembolization, transarterial chemoembolization (TACE), hepatocellular carcinoma, HCC, liver cancer, liver tumor, liver neoplasm and with the assistance of manual searching. Data of the included literature were merged and the patients were divided into TARE group and TACE group according to the different treatments. The data of tumor therapeutic response and 1-, 2-, 3-year survival rates were collected. Literature heterogeneity inspection was conducted byQ test. Publication bias was tested by drawing funnel plot and linear regression model.ResultsFive articles were included after screening with the quality of medium to high. There were totally 591 cases with 292 in TARE group and 299 in TACE group. Meta-analysis was conducted using fixed effect model. Tumor therapeutic response was observed better in TARE group, compared with that in TACE group (RR=1.50,P<0.05). The 2-, 3-year survival rates in TARE group were signiifcantly higher than those in TACE group (RR=1.56, 2.04;P<0.05).ConclusionsCompared with TACE, TARE can obviously improve the tumor therapeutic response rate and long-term survival rate of patients with unresectable PLC.
4.Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers.
Cheng-Long LYU ; Hui-Hui LI ; Yong-Jie SHI ; Yu-Jie MAO ; Qing-He GAO ; Hui-Juan YAN ; Lai-Bin ZHANG ; Jie-Li LYU
China Journal of Chinese Materia Medica 2022;47(19):5140-5157
Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.
Angelica sinensis/chemistry*
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Drugs, Chinese Herbal/pharmacology*
;
Plant Roots/chemistry*
;
China
5.Feasibility of radiofrequency ablation for cancer patients with atrial fibrillation.
Yun Song WANG ; Dao Bo LI ; Cheng CHEN ; Yu Shan WEI ; Hai Chen LYU ; Jia Yu HAN ; Ying Xue DONG ; Xiao Meng YIN ; Lian Jun GAO ; Yun Long XIA
Chinese Journal of Cardiology 2021;49(8):790-795
Objective: To analyze the impact of cancer on the recurrence rate of atrial fibrillation (AF) after AF radiofrequency ablation and further evaluate the feasibility of radiofrequency ablation therapy in cancer patients with AF. Methods: This study was a single-center, retrospective study. Cancer patients with AF undergoing radiofrequency ablation for the first time in the First Affiliated Hospital of Dalian Medical University from May 30, 2008 to September 30, 2018 were included (cancer group). AF patients without cancer undergoing radiofrequency ablation for the first time during the same period served as non-cancer group. Clinical data including age, gender, past history, cancer and AF-related parameters, etc. were analyzed. Patients were followed up after radiofrequency ablation. The primary endpoints were AF recurrence or all-cause death. Kaplan-Meier survival analysis was used to analyze the effect of cancers on the recurrence after AF ablation. The multivariate cox regression analysis was further applied to correct for other confounding factors to analyze whether the impact of cancers on the recurrence of atrial fibrillation was statistically significant. Results: A total of 90 patients were enrolled, there were 30 patients in the cancer group (mean age (64.8±6.6) years, 16 (53.3%) males) and 60 patients in the non-cancer group (mean age (63.6±6.2) years, 32 (53.3%) males). Clinical data, such as age, gender, and cancer treatment, were similar between the two groups. During an average follow-up period of (328.7±110.2) days, there were 6 AF recurrences (recurrence rate 20.0%) in the cancer group, and 17 AF recurrences (recurrence rate 28.3%) in the control group. AF recurrence rate was similar between the two groups (P>0.05). During the follow-up period, there was no all-cause death in the two groups. Kaplan-Meier survival analysis showed that cancer was not related to AF recurrence after radiofrequency ablation (P = 0.383). After adjusting for other confounding factors, the multivariate Cox regression analysis showed that cancer was not an independent predictor of AF recurrence after radiofrequency ablation (HR=0.508, 95%CI: 0.192-1.342, P = 0.172). Conclusions: The combination of cancer has no impact on the recurrence of AF after radiofrequency ablation. For cancer patients with AF, radiofrequency ablation therapy can be considered as a feasible heart rhythm control treatment strategy.
6.Clinicopathological characteristics and differential diagnosis of 6 cases of congenital granular cell tumor.
Long CHENG ; Kun FU ; Ning GAO ; Jing Hua CAI ; Wei Jing XU ; Kang Yan LIU ; Han LU ; Xin Quan LYU ; Li WANG ; Wei HE
Chinese Journal of Stomatology 2022;57(4):410-414
To provide references for the diagnosis and treatment of congenital granular cell tumor (CGCT), by comprehensive analysis of the clinical data, histopathological and immunohistochemical results. Patients with CGCT were involede, from March 2015 to November 2020, at the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Zhengzhou University. A total of 6 children, aged 3-16 days, 1 male and 5 female, 5 maxillary and 1 mandibular, with maximum tumor diameter of 6-70 mm, were included. The lesions of CGCT were single and connected to the alveolar ridge by a pedicle. The surface of the tumor was covered with a vascular network, and two cases had ulcers on the surface of the tumor. All 6 cases had the tumor removed surgically and there was no recurrence or metastasis in the follow-up visit. Although CGCT is rare, it is a benign tumor and generally does not recur or metastasize after surgery, and has a good prognosis. The prenatal imaging, clinical manifestations after delivery, pathological characteristics and immunohistochemical analyses may provide reference for early diagnosis and treatment of CGCT.
Child
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Diagnosis, Differential
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Female
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Gingival Neoplasms/surgery*
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Granular Cell Tumor/surgery*
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Humans
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Male
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Pregnancy
7.The effects of robotic-assisted versus laparoscopic-assisted radical right hemicolectomy on short-term outcome and long-term prognosis based on propensity score matching.
Xing Qi ZHANG ; Shou Gen CAO ; Xiao Dong LIU ; Ze Qun LI ; Yu Long TIAN ; Jian Fei XU ; Cheng MENG ; Yi LI ; Xiao Jie TAN ; Shang Long LIU ; Dong GUO ; Xue Long JIAO ; Yu LI ; Dong CHEN ; Liang LYU ; Jian ZHANG ; Hai Tao JIANG ; Zhao Jian NIU ; Yan Bing ZHOU
Chinese Journal of Surgery 2022;60(2):148-153
Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.
Colectomy
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Colonic Neoplasms/surgery*
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Female
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Humans
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Laparoscopy
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Male
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Prognosis
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Propensity Score
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Retrospective Studies
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Robotic Surgical Procedures
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Treatment Outcome
8.Mori Folium Improves Glucose and Lipid Metabolism Disorders in Rats with Type 2 Diabetes Mellitus by Regulating PI3K/Akt/PPARα/CPT-1 Pathway
Hong-yu DAI ; Jing-kang WANG ; Chen WANG ; Lu SHI ; Yu-hui DUAN ; Yong-cheng AN ; Ying-lan LYU ; Hui-min LI ; Long CHENG ; Chang-hao HE ; Hui-lin ZHANG ; Yan HUANG ; Wan-xin FU ; Zhen-qing LIU ; Bao-sheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(7):105-112
ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus (T2DM) through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 (PI3K/Akt/PPARα/CPT-1) signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin (STZ). The model rats were randomly divided into a model group, a metformin (0.2 g·kg-1) group, and a Mori Folium water extract (4.0 g·kg-1) group according to blood glucose and body weight. In the 8-week administration, fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin (HE) staining and oil red O staining. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum were measured by biochemical methods. Western blot (WB) was used to quantitatively detect the protein expression of p-PI3K,PI3K,p-Akt,Akt,PPARα,and CPT-1 in the rat liver. ResultAfter 8-week administration, the blood glucose of rats was higher in the model group than that in the control group (P<0.01), and lower in the Mori Folium water extract group than that in the model group (P<0.01). The results of HE staining showed that the liver tissue structure of the control group was complete, and the hepatocytes were arranged radially around the central vein, while the hepatocyte injury in the model group was obvious. Compared with the model group, the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group, and no lipid droplets in the hepatocytes were observed, while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC, TG, LDL-C, AST, and ALT in the model group were significantly higher than those in control group (P<0.01). The levels of TC, TG, LDL-C, AST, and ALT in the Mori Folium water extract group were significantly lower than those in the model group (P<0.05,P<0.01). WB showed that the protein expression of p-PI3K/PI3K, p-Akt/Akt, PPARα, and CPT-1 in the model group were lower than those in the control group (P<0.01). Mori Folium water extract could increase the protein expression of p-PI3K/PI3K, p-Akt/Akt, PPARα, and CPT-1 (P<0.05 or P<0.01). ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.
9.Human Serum-derived Extracellular Vesicles Protect A549 from PM
Qiu Lian ZHOU ; Yu Zheng BAI ; Juan GAO ; Yi DUAN ; Yi Cheng LYU ; Long Fei GUAN ; Kenneth ELKIN ; Yu Ling XIE ; Zheng JIAO ; Hong Yun WANG
Biomedical and Environmental Sciences 2021;34(1):40-49
Objective:
Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM
Methods:
EVs were isolated from the serum of healthy subjects, quantified
Results:
PM
Conclusions
EVs treatment promotes cell survival and attenuates PM
A549 Cells
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Air Pollutants/toxicity*
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Apoptosis/drug effects*
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Cell Survival/drug effects*
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Extracellular Vesicles
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Humans
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Male
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Middle Aged
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Particulate Matter/toxicity*
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Protective Agents/pharmacology*
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Proto-Oncogene Proteins c-akt/metabolism*
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Serum
10.Rutin Promotes Browning of 3T3-L1 Preadipocytes and Its Mechanism
Yinglan LYU ; Long CHENG ; Lu SHI ; Hongyu DAI ; Yuhui DUAN ; Yongcheng AN ; Huimin LI ; Chen WANG ; Changhao HE ; Yan HUANG ; Huilin ZHANG ; Wanxin FU ; Yanyan MENG ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):137-143
ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 (CCK-8) assay was used to detect the effect of different concentration of rutin (3.125, 6.25, 12.5, 25, 50, 100, 200 μmol·L-1) on 3T3-L1 cell activity, and Western blot to examine the effect of rutin (12.5, 25, 50 μmol·L-1) on the expression of thermogenesis-associated proteins uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in adipocytes. After the optimal concentration of rutin was determined, the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining, and the expression of nuclear respiratory factor 1 (NRF1), nuclear respiratory factor 2 (NRF2) and mitochondrial transcription factor A (TFAM), which were the landmark proteins of mitochondrial biosynthesis, was detected by Western blot. ResultCompared with the blank group, 200 μmol·L-1 rutin inhibited 3T3-L1 cell activity (P<0.01). Compared with the blank group, at the concentration of 12.5, 25, 50 μmol·L-1 rutin significantly promoted the expression of thermogenesis-associated proteins (UCP1, PRDM16, and PGC-1α) (P<0.01), which was determined as the optimal concentration. Compared with the blank group, 50 μmol·L-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells (P<0.01) and the expression of the markers of mitochondrial biosynthesis (NRF1, NRF2, and TFAM) (P<0.01). In addition, 50 μmol·L-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes (P<0.01). ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins (UCP1, PRDM16, and PGC-1α) and markers of mitochondrial biosynthesis (NRF1, NRF2, and TFAM), thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.